OBJECTIVES: 1. To complete animal toxicity projects now in progress (chronic toxicity studies in rats and squirrel monkeys). Rat toxicity studies with a high dose of beta-glycerophosphate (beta-GP) have been carried out for a period of 8 months without signs of toxicity. The monkey project is going on for a period of 9 months and should be completed after 12 months. 2. Our studies in rodents have shown increased hepatic lecithin synthesis and secretion into bile during beta-GP administration. It has been demonstrated that synthesis of the biliary of linoleic sub-species of lecithin has been stimulated but further studies are now in progress to study its effect on the serum or arachidonic sub-species of hepatic lecithin. 2. To initiate studies on the mechanism by which beta-GP stimulates synthesis of hepatic lecithin. Labelled beta-GP is not available from commercial sources, however the Unilever Research Laboratorium in the Netherlands and a biochemist in Prof. W. Simmonds' Department of Physiology in Perth, Australia, have initiated the synthesis of a double labelled (14C, 32P) beta-GP. Rat liver perfusion in vitro and in vivo techniques are set up to study the effects of beta-GP on lipid metabolism as soon as the radioisotopes can be made available. 3.1. Our experiments have shown that oral beta-GP administration decreased significantly the incidence of cholesterol gallstones in an experimental mouse model. This effect will be evaluated more precisely by quantitative evaluations (amounts of cholesterol solubilized using radioactive cholesterol). 3.2. The effect on prevention of stone formation by beta-GP during feeding with Tepperman's lithogenic diet will be evaluated in mice. 4. Short term studies in human volunteers and in patients with a T-tube in the common duct for therapeutic purposes, will be initiated to quantitate the effect of beta-GP on the biliary lipids (phospholipids, cholesterol and bile salts). BIBLIOGRAPHIC REFERENCE: Raheja, K. L. and W. G. Linscheer and E. C. Regensburger: Dissolution of cholesterol gallstones in mice by oral administration of beta-glycerophosphate. Gastroenterology 70, 973, 1976.